Effect of Longer-term Adrenal Suppression Using Low Dose Hydrocortisone on Androgen Overproduction

July 17, 2018 updated by: Christine Burt Solorzano, University of Virginia

Effect of Longer-term Adrenal Suppression Using Low Dose Hydrocortisone on Androgen Overproduction in Overweight Early Pubertal Girls With Androgen Excess (CBS0004)

This study will test whether longer-term suppression of adrenal function can ameliorate androgen (male hormone) overproduction in overweight early pubertal girls with androgen excess. The investigators hypothesize that suppression of nighttime adrenocorticotropin hormone (ACTH) production by 12 weeks of evening oral hydrocortisone administration will improve androgen levels in girls with adrenal androgen overproduction. Specifically, this intervention will improve androgen levels after adrenal stimulation testing with ACTH or ovarian stimulation testing with recombinant human chorionic gonadotropin (rhCG).

Study Overview

Study Type

Interventional

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Center for Research in Reproduction

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years to 16 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Overweight(>85th BMI%) females
  • Early puberty defined by Tanner 1-2 breast development (expected age range 7-16)
  • Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage)
  • Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated luteinizing hormone (LH), lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (SHBG)

Exclusion Criteria:

  • Age < 7 or > 16 y
  • Inability to comprehend what will be done during the study or why it will be done
  • BMI-for-age < 5th percentile
  • Positive pregnancy test or lactation.
  • Screening labs outside of age-appropriate normal range (Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory error)
  • Morning cortisol < 5 µg/dL or history of Cushing syndrome or adrenal insufficiency
  • History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 295 ng/dL, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-hydroxyprogesterone will be collected during the follicular phase, or ≥ 40 days since last menses if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone >295 mg/dL is confirmed on repeat testing, an ACTH-stimulated 17-hydroxyprogesterone <1000 ng/dL will be required for study participation.
  • Total testosterone > 150 ng/dL, which suggests the possibility of a virilizing neoplasm
  • DHEAS greater than the upper limit of age-appropriate normal range (mild elevations may be seen in polycystic ovary syndrome (PCOS) and adolescent hyperandrogenemia (HA), and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in these groups)
  • Virilization
  • Previous diagnosis of diabetes, fasting glucose ≥126 mg/dL, or a hemoglobin A1c ≥6.5%
  • Abnormal thyroid stimulating hormone (TSH) for age. Subjects with stable and adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded.
  • Abnormal prolactin. Mild elevations may be seen in overweight girls, and elevations <1.5 times the upper limit of normal will be accepted in this group.
  • Persistent hematocrit <36% and hemoglobin <12 g/dL. Subjects with a mildly low hematocrit (33-36%) will be asked to take iron in the form of ferrous gluconate for up to 60 days. Subjects weighing ≤ 36 kg will take one 300-325 mg tablet oral ferrous gluconate daily (containing 36 mg elemental iron);subjects weighing >36 kg will take two 300-325 mg tablets oral ferrous gluconate daily (containing 36 mg elemental iron each). They will return to the Clinical Research Unit (CRU) after 30-60 days of iron therapy to have their hemoglobin or hematocrit rechecked and will proceed with the remainder of the study if it is ≥12 g/dL or ≥36%, respectively.
  • Persistent liver test abnormalities, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Mild elevations may be seen in overweight girls, so elevations <1.5 times the upper limit of normal will be accepted in this group.
  • Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
  • Abnormal sodium, potassium, or bicarbonate concentrations, or elevated creatinine concentration (confirmed on repeat)
  • No medications known to affect the reproductive system or glucose metabolism can be taken in the 3 months prior to the study. Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, and psychotropics.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: hydrocortisone, dexamethasone, Cosyntropin (ACTH), rhCG
12 weeks hydrocortisone, dexamethasone, and Cosyntropin (ACTH) to perform standardized adrenal stimulation testing; dexamethasone, and rhCG to perform standardized ovarian stimulation testing
10mg/m2/per day PO at bedtime (X12 weeks)
1 mg PO twice
250 micrograms IV twice
Other Names:
  • Tetracosactide
25 mcg IV twice
Other Names:
  • (Ovidrel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in free testosterone or 17-hydroxyprogesterone levels after ACTH and rhCG administration respectively, before and after hydrocortisone administration for 12 weeks
Time Frame: 12 weeks after hydrocortisone administration
12 weeks after hydrocortisone administration

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in adrenal and ovarian steroid precursors after ACTH and rhCG; body composition via air displacement plethysmography, BMI, and glucose tolerance testing results; baseline and after 12 weeks of hydrocortisone administration
Time Frame: 12 weeks after hydrocortisone administration
12 weeks after hydrocortisone administration
Morning cortisol
Time Frame: 72 hours following discontinuation of hydrocortisone
72 hours following discontinuation of hydrocortisone

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2018

Primary Completion (Actual)

July 17, 2018

Study Completion (Actual)

July 17, 2018

Study Registration Dates

First Submitted

August 22, 2011

First Submitted That Met QC Criteria

August 23, 2011

First Posted (Estimate)

August 24, 2011

Study Record Updates

Last Update Posted (Actual)

July 19, 2018

Last Update Submitted That Met QC Criteria

July 17, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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